ABSTRACT Alzheimer?s disease (AD) and related dementia (ADRD) are irreversible, progressive brain disorders that slowly destroy memory, thinking, and other neuro-cognitive skills in older adults. More people die from ADRD in the US than breast and prostate cancer combined. Medical care for about 50 million ADRD cases worldwide is an enormous financial burden, equivalent to the 18th largest economy in the world. A major challenge for countries like China is that with industrialization and rapid growth of the economy, the prevalence of unhealthy lifestyle and metabolic factors has increased, which contributes to an increased rate of ADRD. Chinese have a much higher risk of stroke and diabetes than Americans, and these traits have not been well-studied in connection with ADRD. Predictive and affordable biomarkers for ADRD risk are needed to tackle dementia in in low- and middle-income regions. The goal of this Sino-US study is to validate neurophysiological biomarkers for individualized prediction of MCI in Kentucky and Beijing cohorts using an ultimate clinical outcome measure, conversion to mild cognitive impairment (MCI), an early stage of ADRD. The cross-national research team will test the central hypothesis that healthy older individuals who have MCI-like neurophysiological brain signatures have high-risk of MCI conversion induced by ADRD. The hypothesis is based on promising results from our longitudinal pilot study, i.e. individuals who convert to MCI have MCI-like brainwave signatures about 5 years before conversion. The team has previously identified unique brainwaves during the Bluegrass memory task in patients with amnestic MCI (aMCI; memory-related impairment) using the Kentucky cohort. Here, matching standardized protocols will be applied in the two Sino & US cohorts. The NIA-funded University of Kentucky Alzheimer?s Disease Center has been following a cohort of 500 cognitively intact older adults to autopsy for the past 35 years, along with multiple ADRD biomarker banks. The Beijing cohort is part of a national longitudinal cohort for ADRD early detection. Specifically, Aim 1 will determine whether individual baseline memory-related neuromarkers are predictors for MCI conversion. Neurocognitive measures will be collected at the baseline and 3-year follow-up in both healthy cohorts to test the hypothesis that the converters to MCI already show abnormality of brain activity patterns at the baseline. Aim 2 will determine whether the neuromarkers differentiate between amnestic versus non-amnestic MCI. The hypothesis that the distinct neurophysiological responses are associated with vascular diseases induced MCI will be tested. Aim 3 will validate the neuromarkers by correlating them with established ADRD biomarkers, and neuropsychological scores from baseline to follow-up. Using gold-standard AD biomarkers, the hypothesis that individuals who are A-positive have an increased rate of longitudinal change in neurophysiological biomarkers. These noninvasive and affordable risk markers, once validated and replicated, will be suitable for large-scale use. The propose study will build a base for research networking that can be used for future prevention and treatment.